The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

Rossella Baggetta, Marco De Andrea, Grazia Rosaria Gariano, Michele Mondini, Massimo Rittà, Patrizia Caposio, Paola Cappello, Mirella Giovarelli, Marisa Gariglio, Santo Landolfo

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Abstract

The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-κB is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation.

Original languageEnglish (US)
Pages (from-to)2182-2189
Number of pages8
JournalEuropean Journal of Immunology
Volume40
Issue number8
DOIs
Publication statusPublished - Aug 2010

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Keywords

  • Chemokines
  • IFI16
  • IFN
  • Inflammation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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